Rapamycin was originally isolated from a bacterium found on Rapa Nui, the indigenous name for Easter Island. Rapamycin (Rapamune®, Wyeth Ayerst, sirolimus) is a specific inhibitor of the target of rapamycin (TOR). Rapamycin is also a powerful suppressor of the human immune system, as cell anti proliferating drug, so commonly given to organ[Kidney] transplant patients[6mg as soon as after transplant, then 2mg daily for 2-3months as maintenance dose] to help to prevent the rejection of transplanted organs, used with cardiac drug eluting stents[to prevent proliferation of endothelial cells after stent] and may be used as a cancer adjuvant therapy, and also in autosomal dominent polycystic kidney disease. The drug is very costly approximately costs Rs12000/=, in Indian currency a month. Orthologue (mTOR), is also referred to as FKBP12-rapamycin associated protein (FRAP), rapamycin and FKBP12 target (RAFT), rapamycin target (RAPT), or sirolimus effector protein (SEP). mTOR lies downstream of IGF and has been implicated in several pathways that contribute to tumorigenesis, such as translation initiation and cap-dependent translation. The protein kinase TOR genes (TOR1 and TOR2) were first identified in the early 1990s in a screen for rapamycin-resistant yeast mutants1 . Rapamycin forms a complex with the immunophilin FK506 binding protein-12 (FKBP12), which binds to the FKBP12-rapamycin binding (FRB) domain of mTOR and inhibits its kinase activity. Rapamycin thus can inhibit the growth of a broad spectrum of cancers including rhabdomyosarcoma, neuroblastoma, glioblastoma, small cell lung carcinoma, osteosarcoma, pancreatic cancer, leukaemia, B-cell lymphoma, and breast and colon cancer-derived cells2The rapamycin analogues, CCI-779 (Wyeth-Ayerst, PA, USA), RAD001 (Novartis, Switzerland), and AP23573 (Ariad Pharmaceuticals, MA, USA) have shown promise in clinical trials3 .mTOR functions by integrating extracellular signals (growth factors and hormones), with amino-acid availability and intracellular energy status to control translation rates and additional metabolic processes4 .mTOR enhances translation initiation in part by phosphorylating two major targets, the eIF4E binding proteins (4E-BPs) and the ribosomal protein S6 kinases (S6K1 and S6K2) that cooperate to regulate translation initiation rates.5 In Peutz Jeghers syndrome, Tuberous Sclerosis, and other diseases where PTEN is inactivated, the use of rapamycin as a clinical means to reverse the effect of elevated mTOR activity is an attractive option5. These diseases are distinct from other hamartoma-associated disorders (such as VHL syndrome) since they have an established molecular link to mTOR. Earlier studies demonstrated that PTEN-inactivated tumour cells exhibit enhanced sensitivity to the rapamycin analog CCI-7796 More recently, several studies have shown that rapamycin treatment, in combination with other chemotherapeutic drugs, can lead to enhanced selective killing of cancer cells. In particular, the protein tyrosine kinase (PTK) inhibitor, Imatinib (Gleevec, STI571) synergises with rapamycin to inhibit BCR/ABL transformed cells7 . The effect of rapamycin may be enhanced as a result of Imatinib-induced Akt/mTOR signaling, a complication that is thought to lead to Imatinib resistance. Rapamycin can also synergise with paclitaxel, carboplatin, and vinorelbine to induce apoptosis in breast cancer cells8 Cisplatin-induced apoptosis of A549 lung cancer cells is also significantly enhanced when combined with RAD0019 . This could be in part due to reduced translation of p53-activated p21 mRNA in A549 and MCF7 cells treated with RAD001, thereby allowing the dosage of cisplatin to be reduced Also, the use of theEGFR/VEGFR inhibitor, AEE788, in combination with RAD001 greatly decreased tumour growth in glioma xenografts (Goudar et al, 2005). Furthermore, targeting the glycolytic pathway in combination with mTOR inhibition may also be useful in cases where DNA-damaging agents are less efficient in inhibiting growth and promoting apoptosis of cancer cells10 .Aging is the progressive, universal decline first in functional reserve and then in function that occurs in organisms over time. Aging is heterogeneous. It varies widely in different individuals and in different organs within a particular individual. Aging is not a disease; however, the risk of developing disease is increased, often dramatically, as a function of age. The biochemical composition of tissues changes with age; physiologic capacity decreases, the ability to maintain homeostasis in adapting to stressors declines, and vulnerability to disease processes increases with age. After maturation, mortality rate increases exponentially with age

Some Theories of Aging11Hypothesis How It May Work- Genetic Aging is a genetic program activated in post-reproductive life when an individual’s evolutionary mission is accomplishedOxidative stressAccumulation of oxidative damage to DNA, proteins, and lipids interferes with normal function and produces a decrease in stress responsesMitochondrial dysfunction A common deletion in mitochondrial DNA with age compromises function and alters cell metabolic processes and adaptability to environmental changeHormonal changes The decline and loss of circadian rhythm in secretion of some hormones produces a functional hormone deficiency state

Telomere shortening Aging is related to a decline in the ability of cells to replicateDefective host defenses The failure of the immune system to respond to infectious agents and the over activity of natural immunity create vulnerability to environmental stressesAccumulation of senescent cells Renewing tissues become dysfunctional through loss of ability to renew

So it is not well understood how rapamycin actually prolongs life affecting the ageing process and how its connected to calorie restriction and ageing? Through sirolimus effectors protein (SEP)? Then ageing process can be slowed by a drug therapy starting at an advanced age? should healthy individuals over age 50 consider taking rapamycin to slow his/her ageing?. However it is too costly therapy then. Moreover there are many adverse drug reactions of rapamycin like opportunistic infections, lynmhocele lymphoedema, sepsis, tachycardia hepatotoxicity susceptibilities to lymhoma and other malignancies, exfoliative dermatities azospermia to name a few. Mice are known to live longer if fed a calorie-restricted diet that is close to starvation levels, but this would be very difficult for a person to maintain. what should be the dose?